Synthetic receptors for hydrosulfide

ABSTRACT

A method for detecting for the presence of H2S or HS− anion in a system, comprising contacting a sample from the system with a compound, or a protonate or salt thereof, having a structure represented by:wherein Y represents an aromatic group or a substituted aromatic group;n is 1 or 2;R is independently H, alkyl, substituted alkyl, a polyether moiety, carboxyl, substituted carboxyl, carbamate, substituted carbonate, carbonyloxy, alkoxy, substituted alkoxy, haloalkyl, halogen, nitro, amino, amido, aryloxy, cyano, hydroxyl, or sulfonyl;R1 is H, substituted lower alkyl, lower alkyl, substituted aralkyl or aralkyl;R2 is selected from H, acyl, substituted aralkyl, aralkyl, phosphonyl, —SO2R3; —C(O)R5; —C(O)OR7 or —C(O)NR9R10;R3; R5; R7; R9 and R10 are each independently selected from H, substituted lower alkyl, lower alkyl, substituted aralkyl, aralkyl, substituted aryl or aryl.

CROSS REFERENCE TO RELATED APPLICATION

This application is a divisional of U.S. application Ser. No.15/612,848, filed on Jun. 2, 2017, which claims the benefit of U.S.Provisional Appl. No. 62/345,619, filed on Jun. 3, 2016, which isincorporated herein by reference.

ACKNOWLEDGMENT OF GOVERNMENT SUPPORT

This invention was made with government support under grant CHE-1454747awarded by the National Science Foundation and grant R01-GM087398awarded by the National Institutes of Health. The government has certainrights in the invention.

BACKGROUND

Hydrogen sulfide (H₂S), although generally known for its toxicity andcharacteristic odor, is now recognized as an important signalingmolecule with diverse biological roles. The biological roles of H₂Srange from roles in angiogenesis to wound healing. In mammals, H₂Sproduction is derived primarily from three enzymes:cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and3-mercaptopyruvate sulfotransferase (3-MST). The expression of theseenzymes in different tissues suggests a broad importance andsignificance of H₂S in the cardiovascular, circulatory, respiratory,urinary, and nervous systems. Abnormal H₂S regulation, however, has beenassociated with hypertension, diabetes, as well as various diseases ofmental deficiency including Down's syndrome and Alzheimer's disease. Inaddition to the pathophysiological conditions associated with H₂Smisregulation, H₂S can also act on specific cellular targets, includingheme proteins, cysteine residues on KATP channels, nitric oxide, andother emerging targets.

Complicating investigations into biological H₂S, the pK_(a) of H₂S (7.0)ensures that both the neutral (H₂S) and monoanionic (HS⁻) forms arepresent under physiological conditions, leading to significant andunresolved questions on the specific chemistry and recognition eventsassociated with the individual protonation states. Importantly, theserecognition events in sulfide transport rely on non-covalent, reversibleinteractions with HS⁻ rather than metal coordination or interaction withthe sulfane-sulfur pool.

Despite the importance of H₂S, current methods of detection are plaguedby irreversibility, which presents a significant problem in developingchemical tools that provide real-time information on biologicalprocesses, suggesting a supramolecular (i.e., reversible) approach tohydrosulfide binding would represent an important contribution.

SUMMARY

Disclosed herein is a method for detecting for the presence of H₂S orHS⁻ anion in a system, comprising contacting a sample from the systemwith a compound, or a protonate or salt thereof, having a structurerepresented by:

wherein Y represents an aromatic group or a substituted aromatic group;

n is 1 or 2;

R is independently H, alkyl, substituted alkyl, a polyether moiety,carboxyl, substituted carboxyl, carbamate, substituted carbonate,carbonyloxy, alkoxy, substituted alkoxy, haloalkyl, halogen, nitro,amino, amido, aryloxy, cyano, hydroxyl, or sulfonyl;

R¹ is H, substituted lower alkyl, lower alkyl, substituted aralkyl oraralkyl;

R² is selected from H, acyl, substituted aralkyl, aralkyl, phosphonyl,—SO₂R³; —C(O)R⁵; —C(O)OR⁷ or —C(O)NR⁹R¹⁰;

R³; R⁵; R⁷; R⁹ and R¹⁰ are each independently selected from H,substituted lower alkyl, lower alkyl, substituted aralkyl, aralkyl,substituted aryl or aryl.

Also disclosed herein is a method for detecting for the presence of H₂Sor HS⁻ anion in a system, comprising contacting a sample from the systemwith a compound, or a protonate or salt thereof, having a structurerepresented by:

wherein Y represents a substituted aromatic group or an aromatic group;

each R¹⁵ is independently H, alkyl, substituted alkyl, a polyethermoiety, carboxyl, substituted carboxyl, carbamate, substitutedcarbonate, carbonyloxy, alkoxy, substituted alkoxy, haloalkyl, halogen,nitro, amino, amido, aryloxy, cyano, hydroxyl, or sulfonyl;

each X is independently halogen, alkoxy, substituted alkoxy, alkyl,substituted alkyl or a polyether moiety; and

m is 0 to 5.

Further disclosed herein is a method for detecting for the presence ofH₂S or an anionic sulfide species in a system, comprising contacting asample from the system with a compound, or a protonate or salt thereof,having a structure that includes at least one moiety configured forreversible, non-covalent binding of the anionic sulfide species.

Also disclosed herein is a compound, or a protonate or salt thereof,having a structure represented by:

each R¹⁵ is independently H, alkyl, substituted alkyl, a polyethermoiety, carboxyl, substituted carboxyl, carbamate, substitutedcarbonate, carbonyloxy, alkoxy, substituted alkoxy, haloalkyl, halogen,nitro, amino, amido, aryloxy, cyano, hydroxyl, or sulfonyl;

each X is independently halogen, alkoxy, substituted alkoxy, alkyl,substituted alkyl or a polyether moiety;

m is 0 to 5; and

wherein R⁵⁰, R⁵¹, R⁵², R⁵³, R⁵⁴ and R⁵⁵ are each independently selectedfrom hydrogen, alkyl, substituted alkyl, a polyether moiety, carboxyl,substituted carboxyl, carbamate, substituted carbonate, carbonyloxy,alkoxy, substituted alkoxy, haloalkyl, halogen, nitro, amino, aryloxy,cyano, hydroxyl, or sulfonyl.

The foregoing will become more apparent from the following detaileddescription, which proceeds with reference to the accompanying figures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A. Complete protein structure of HSC (PDB:3TDX) showing fiveindividual channels. The bound anion is represented as a yellow sphere.FIG. 1B. Enlargement of the binding pocket showing short contacts to His(2.980 Å), Thr (3.010 Å), Leu (3.725 Å) and Val (3.619 and 4.610 Å).External helices not involved in the highlighted short contacts areexcluded for clarity. FIG. 1C. Synthetic receptors 1-3.

FIG. 2A. Scheme showing HS⁻ host-guest equilibrium. FIG. 2B.Representative UV-Vis difference titration of NBu₄SH with 10 μM 2 inMeCN and fit to a 1:1 binding isotherm (inset). FIG. 2C. 1H NMR spectraof a titration of 0.988 mM 1 with NBu₄SH in 10% MSOd6/CD3CN.

FIG. 3A. Reversibility reaction scheme. FIG. 3B. 1H NMR spectrum of a1.0 mM solution of 1 in 10% DMSO-d₆/CD₃CN. FIG. 3C. Treatment with 2equiv. of NBu₄SH. FIG. 3D. Addition of 4 equiv. Zn(OAc)₂. Each insetshows the ¹³C{¹H} resonances corresponding to the alkyne region of 1.

FIG. 4. ORTEP representation showing selected hydrogen bond distances.Hydrogens not interacting with the bound HS⁻ are removed for clarity.

FIG. 5 is a schematic of a chemical sensing system.

FIG. 6 is a cross-section of an illustrative embodiment of a chemicalsensor disclosed herein.

DETAILED DESCRIPTION

Current tools for the detection of HS⁻/H₂S utilize non-reversiblereaction based chemistry. Examples include nucleophilic attack by HS⁻,reduction of an azide or nitro moiety, and metal coordination. Thedevelopment of small molecule fluorescent probes that utilizesupramolecular interactions will greatly expand the ability ofresearchers to investigate the role of hydrogen sulfide in biologicalsystems without the disruption of endogenous concentrations of H₂S.

The receptor compounds and methods disclosed herein can be applied tobiological fluorescent probes or sensors for HS⁻/H₂S. The receptorcompounds and methods disclosed herein can also be utilized for thestorage, transport, and delivery of HS⁻/H₂S for possible therapeuticapplications or scientific investigations.

A new method of detection for hydrosulfide anion (HS⁻) and hydrogensulfide (H₂S) is disclosed herein. This method utilizes reversible,supramolecular binding interactions which have not been previouslyreported. The supramolecular detection of HS⁻/H₂S is a novel strategywhich allows for the detection of HS⁻/H₂S without disrupting or alteringthe analyte concentration during experimentation.

The receptors disclosed herein feature hydrogen bond donors to targetthe anionic portion of hydrosulfide and a hydrogen bond acceptor (orsuitable pocket of electron density) to accommodate the very slightlyacidic hydrogen atom. In particular, the receptors bind anions throughtunable urea NH hydrogen bonds, and the central core incorporates anadditional hydrogen bond donating arene (compounds 1, 4, 5 and 6 below)or a hydrogen bond accepting pyridine group (compounds 2 and 3 below).

In particular, disclosed herein is a series of bis(ethynylaniline)derivatives capable of binding hydrosulfide anion with associationconstants as high as 90,300±8700 M⁻¹, representing the first reversiblebinding of the hydrosulfide anion in a synthetic receptor. ¹H NMR andUV-Vis spectroscopy both indicate a greater selectivity for HS⁻ in thepyridine core; however, the phenyl core shows a larger binding affinity,likely due to an additional hydrogen-bonding motif. The preference forthe phenyl core highlights the unexpected conclusion that a C—H . . . Scontact is favored over an N: . . . H—S contact by up to 0.9 kcal mol⁻¹.CH hydrogen bond donors are important components in targetinghydrosulfide reversibly, and receptors featuring appropriately polarizedCH donors should exhibit enhanced selectivity and stronger binding. Theresults disclosed herein support reversible binding of HS⁻, rather thancovalent modification or deprotonation. The basic science of syntheticnon-covalent binding of sulfide will help to identify new targetproteins for the binding of sulfide, while also informing detectionstrategies that do not rely on irreversible covalent modification offluorescent platforms for sulfide detection.

Compounds 1-6 (see below) have been shown to reversibly bind HS⁻ usinghydrogen bonds. Compound 1 and 4-5 utilize four urea NH donors and onearyl CH donor. Compounds 2-3 utilize four urea NH donors and the freepyridine electrons as a hydrogen bond acceptor. Both strategies haveproven to be viable platforms for HS⁻ detection. Compound 6 utilizesfour NH donors and two aryl CH donors.

The following explanations of terms and methods are provided to betterdescribe the present compounds, compositions and methods, and to guidethose of ordinary skill in the art in the practice of the presentdisclosure. It is also to be understood that the terminology used in thedisclosure is for the purpose of describing particular embodiments andexamples only and is not intended to be limiting.

“Acyl” refers group of the formula RC(O)— wherein R is an organic group.

The term “aliphatic” includes alkyl, alkenyl, alkynyl, halogenated alkyland cycloalkyl groups as described above. A “lower aliphatic” group is abranched or unbranched aliphatic group having from 1 to 10 carbon atoms.

The term “alkoxy” refers to a straight, branched or cyclic hydrocarbonconfiguration and combinations thereof, including from 1 to 20 carbonatoms, preferably from 1 to 10 carbon atoms, more preferably from 1 to 4carbon atoms, that includes an oxygen atom at the point of attachment.An example of an “alkoxy group” is represented by the formula —OR, whereR can be an alkyl group, optionally substituted with, e.g., an alkenyl,alkynyl, aryl, aralkyl, cycloalkyl, halogenated alkyl, orheterocycloalkyl group as described herein. Suitable alkoxy groupsinclude methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy,sec-butoxy, tert-butoxy cyclopropoxy, cyclohexyloxy, and the like.

The term “alkyl” refers to a branched or unbranched saturatedhydrocarbon group of 1 to 24 carbon atoms, such as methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, pentyl, hexyl, heptyl,octyl, decyl, tetradecyl, hexadecyl, eicosyl, tetracosyl and the like. A“lower alkyl” group is a saturated branched or unbranched hydrocarbonhaving from 1 to 6 carbon atoms. Preferred alkyl groups have 1 to 4carbon atoms. Alkyl groups may be “substituted alkyls” wherein one ormore hydrogen atoms are substituted with a substituent such as halogen,cycloalkyl, alkoxy, amino, hydroxyl, aryl, alkenyl, or carboxyl. Forexample, a lower alkyl or (C₁-C₆)alkyl can be methyl, ethyl, propyl,isopropyl, butyl, iso-butyl, sec-butyl, pentyl, 3-pentyl, or hexyl;(C₃-C₆)cycloalkyl can be cyclopropyl, cyclobutyl, cyclopentyl, orcyclohexyl; (C₃-C₆)cycloalkyl(C₁-C₆)alkyl can be cyclopropylmethyl,cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl,2-cyclopropylethyl, 2-cyclobutylethyl, 2-cyclopentylethyl, or2-cyclohexylethyl; (C₁-C₆)alkoxy can be methoxy, ethoxy, propoxy,isopropoxy, butoxy, iso-butoxy, sec-butoxy, pentoxy, 3-pentoxy, orhexyloxy; (C₂-C₆)alkenyl can be vinyl, allyl, 1-propenyl, 2-propenyl,1-butenyl, 2-butenyl, 3-butenyl, 1,-pentenyl, 2-pentenyl, 3-pentenyl,4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, or 5-hexenyl;(C₂-C₆)alkynyl can be ethynyl, 1-propynyl, 2-propynyl, 1-butynyl,2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl,1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, or 5-hexynyl;(C₁-C₆)alkanoyl can be acetyl, propanoyl or butanoyl; halo(C₁-C₆)alkylcan be iodomethyl, bromomethyl, chloromethyl, fluoromethyl,trifluoromethyl, 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, orpentafluoroethyl; hydroxy(C₁-C₆)alkyl can be hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, 1-hydroxypropyl, 2-hydroxypropyl,3-hydroxypropyl, 1-hydroxybutyl, 4-hydroxybutyl, 1-hydroxypentyl,5-hydroxypentyl, 1-hydroxyhexyl, or 6-hydroxyhexyl;(C₁-C₆)alkoxycarbonyl can be methoxycarbonyl, ethoxycarbonyl,propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, pentoxycarbonyl, orhexyloxycarbonyl; (C₁-C₆)alkylthio can be methylthio, ethylthio,propylthio, isopropylthio, butylthio, isobutylthio, pentylthio, orhexylthio; (C₂-C₆)alkanoyloxy can be acetoxy, propanoyloxy, butanoyloxy,isobutanoyloxy, pentanoyloxy, or hexanoyloxy.

The term “amine” or “amino” refers to a group of the formula —NRR′,where R and R′ can be, independently, hydrogen or an alkyl, alkenyl,alkynyl, aryl, aralkyl, cycloalkyl, halogenated alkyl, orheterocycloalkyl group described above.

The term “amide” refers to the formula —C(O)NRR′, wherein R and R′independently can be a hydrogen, alkyl, alkenyl, alkynyl, aryl, aralkyl,cycloalkyl, halogenated alkyl, or heterocycloalkyl group describedabove.

The term “aralkyl” refers to an alkyl group that is substituted with oneor more aryl groups (described below). A particular example of anaralkyl group is a benzyl group.

The term “aryl” refers to any carbon-based aromatic group including, butnot limited to, phenyl, naphthyl, etc. The term “aromatic” also includes“heteroaryl groups,” which are defined as aromatic groups that have atleast one heteroatom incorporated within the ring of the aromatic group.Examples of heteroatoms include, but are not limited to, nitrogen,oxygen, sulfur, and phosphorous. The aryl group can be substituted withone or more groups including, but not limited to, alkyl, alkynyl,alkenyl, aryl, halide, nitro, amino, ester, ketone, aldehyde, hydroxy,carboxylic acid, or alkoxy, or the aryl group can be unsubstituted.

“Carbonyl” refers to a radical of the formula —C(O)—.Carbonyl-containing groups include any substituent containing acarbon-oxygen double bond (C═O), including acyl groups, amides, carboxygroups, esters, ureas, carbamates, carbonates and ketones and aldehydes,such as substituents based on —COR or —RCHO where R is an aliphatic,heteroaliphatic, alkyl, heteroalkyl, hydroxyl, or a secondary, tertiary,or quaternary amine. “Carbonyloxy” refers to a group of the —OC(O)Rwhere R is an aliphatic (e.g., alkyl) or aromatic (e.g., aryl) group.

“Carbonate” refers to a group of the formula —OC(O)O—. “Substitutedcarbonate” refers to a group of the formula —OC(O)OR. Likewise, as usedherein the term “carbamate” refers to a group of the formula—OC(O)N(R)—, wherein R is H, or an aliphatic group, such as a loweralkyl group or an aralkyl group.

“Carboxyl” refers to a —COOH radical. Substituted carboxyl refers to—COOR where R is aliphatic, heteroaliphatic, alkyl, heteroalkyl, or acarboxylic acid or ester.

“Optional” or “optionally” means that the subsequently described eventor circumstance can but need not occur, and that the descriptionincludes instances where said event or circumstance occurs and instanceswhere it does not. Optionally substituted groups, such as “substitutedalkyl,” refers to groups, such as an alkyl group, having from 1-5substituents, typically from 1-3 substituents, selected from alkoxy,optionally substituted alkoxy, acyl, acylamino, acyloxy, amino,aminoacyl, aminoacyloxy, aryl, carboxyalkyl, optionally substitutedcycloalkyl, optionally substituted cycloalkenyl, optionally substitutedheteroaryl, optionally substituted heterocyclyl, hydroxy, thiol andthioalkoxy.

The term “phosphoryl” refers to moieties of the formula —P(O)OR—,wherein R may be H, an aliphatic or aromatic moiety, a cation or a lonepair of electrons. Phosphoryl moieties may be further substituted toform phosphoramidates, phosphates and phosphonates.

The term “polyether moiety” may be an oligomer (which is inclusive ofdimers and higher repeating units) or a polymer. Illustrative polyethermoieties include those derived from an aliphatic polyether (e.g.,paraformaldehyde, polyethylene glycol (PEG), polypropylene glycol, andpolytetramethylene glycol, and those derived from an aromatic polyether(e.g., polyphenyl ether or poly(p-phenylene oxide)). A preferredpolyether moiety is derived from PEG, also referred to herein as apoly(ethylene oxide). The PEG may be a straight chain PEG or a branchedPEG. PEG is also inclusive of methoxypolyethylene glycol. In certainembodiments, the number of repeating ethylene oxide units in the PEGmoiety may range from 2 to 50, more particularly from 2 to 10. Thepolyether moiety may be covalently bonded to the core motif viaPEGylation procedures.

The term “sulfonyl” refers to the radical —SO₂—. The sulfonyl group canbe further substituted with a variety of groups to form, for example,sulfonic acids, sulfonamides, sulfonate esters and sulfones.

Protected derivatives of the disclosed compound also are contemplated. Avariety of suitable protecting groups for use with the disclosedcompounds are disclosed in Greene and Wuts Protective Groups in OrganicSynthesis; 3rd Ed.; John Wiley & Sons, New York, 1999.

It is understood that substituents and substitution patterns of thecompounds described herein can be selected by one of ordinary skill inthe art to provide compounds that are chemically stable and that can bereadily synthesized by techniques known in the art and further by themethods set forth in this disclosure.

The structural formulas provided herein include salts of the illustratedcompounds. Such salts can be formed when disclosed host compoundspossess at least one basic group that can form acid-base salts withacids. Examples of basic groups present in exemplary disclosed hostcompounds include amino groups or imino groups. Examples of inorganicacids that can form salts with such basic groups include, but are notlimited to, mineral acids such as hydrochloric acid, hydrobromic acid,sulfuric acid or phosphoric acid. Basic groups also can form salts withorganic carboxylic acids, sulfonic acids, sulfo acids or phospho acidsor N-substituted sulfamic acid, for example acetic acid, propionic acid,glycolic acid, succinic acid, maleic acid, hydroxymaleic acid,methylmaleic acid, fumaric acid, malic acid, tartaric acid, gluconicacid, glucaric acid, glucuronic acid, citric acid, benzoic acid,cinnamic acid, mandelic acid, salicylic acid, 4-aminosalicylic acid,2-phenoxybenzoic acid, 2-acetoxybenzoic acid, embonic acid, nicotinicacid or isonicotinic acid, and, in addition, with amino acids, forexample with α-amino acids, and also with methanesulfonic acid,ethanesulfonic acid, 2-hydroxymethanesulfonic acid,ethane-1,2-disulfonic acid, benzenedisulfonic acid,4-methylbenzenesulfonic acid, naphthalene-2-sulfonic acid, 2- or3-phosphoglycerate, glucose-6-phosphate or N-cyclohexylsulfamic acid(with formation of the cyclamates) or with other acidic organiccompounds, such as ascorbic acid.

Similarly, salts can be formed when disclosed host compounds possess atleast one acidic group that can form acid-base salts with bases.Examples of acidic groups present in exemplary disclosed host compoundsinclude carboxylic acid moieties and sulfonamide groups. Compounds thatinclude at least one acidic group can form an acid-base salts with aninorganic or organic base. Examples of salts formed from inorganic basesinclude salts of the presently disclosed compounds with alkali metalssuch as potassium and sodium, alkaline earth metals, including calciumand magnesium and the like. Similarly, salts of acidic compounds with anorganic base, such as an amine (as used herein terms that refer toamines should be understood to include their conjugate acids unless thecontext clearly indicates that the free amine is intended) arecontemplated, including salts formed with basic amino acids, aliphaticamines, heterocyclic amines, aromatic amines, pyridines, guanidines andamidines. In addition, quaternary ammonium counterions also can be used.

Additionally, the structural formulas herein are intended to cover,where applicable, solvated as well as unsolvated forms of the compounds.“Solvate” refers to a compound physically associated with one or moresolvent molecules. This physical association involves varying degrees ofionic and covalent bonding, including by way of example covalent adductsand hydrogen bonded solvates. In certain instances the solvate will becapable of isolation, for example when one or more solvent molecules areincorporated in the crystal lattice of the crystalline solid. “Solvate”encompasses both solution-phase and isolable solvates. Representativesolvates include ethanol associated compounds, methanol associatedcompounds, and the like. “Hydrate” is a solvate wherein the solventmolecule(s) is/are H₂O. Solvate complexes may be described in shorthandform for example as (1.H₂O)₂, which refers to a hydrate, morespecifically a 2+2 complex of compound 1 with water.

Compounds disclosed herein can be crystallized and can be provided in asingle crystalline form or as a combination of different crystalpolymorphs. As such, the compounds can be provided in one or morephysical form, such as different crystal forms, crystalline, liquidcrystalline or non-crystalline (amorphous) forms. Such differentphysical forms of the compounds can be prepared using, for exampledifferent solvents or different mixtures of solvents forrecrystallization. Alternatively or additionally, different polymorphscan be prepared, for example, by performing recrystallizations atdifferent temperatures and/or by altering cooling rates duringrecrystallization. The presence of polymorphs can be determined by X-raycrystallography, or in some cases by another spectroscopic technique,such as solid phase NMR spectroscopy, IR spectroscopy, or bydifferential scanning calorimetry.

In one embodiment the receptor compounds and salts thereof have theformula

wherein Y represents an aromatic group or a substituted aromatic group;

n is 1 or 2;

R is independently H, alkyl, substituted alkyl, a polyether moiety,carboxyl, substituted carboxyl, carbamate, substituted carbonate,carbonyloxy, alkoxy, substituted alkoxy, haloalkyl, halogen, nitro,amino, amido, aryloxy, cyano, hydroxyl, or sulfonyl;

R¹ is H, substituted lower alkyl, lower alkyl, substituted aralkyl oraralkyl;

R² is selected from H, acyl, substituted aralkyl, aralkyl, phosphonyl,—SO₂R³; —C(O)R⁵; —C(O)OR⁷ or —C(O)NR⁹R¹⁰;

R³; R⁵; R⁷; R⁹ and R¹⁰ are each independently selected from H,substituted lower alkyl, lower alkyl, substituted aralkyl, aralkyl,substituted aryl or aryl.

In a further embodiment the receptor compounds and salts thereof havethe formula

wherein Y represents a substituted aromatic group or an aromatic group;

each R¹⁵ is independently H, alkyl, substituted alkyl, a polyethermoiety, carboxyl, substituted carboxyl, carbamate, substitutedcarbonate, carbonyloxy, alkoxy, substituted alkoxy, haloalkyl, halogen,nitro, amino, amido, aryloxy, cyano, hydroxyl, or sulfonyl;

each X is independently halogen, alkoxy, substituted alkoxy, alkyl,substituted alkyl or a polyether moiety; and

m is 0 to 5.

In certain embodiment of formula I or II, Y is:

wherein R²⁰, R⁵⁰, R⁵¹, R⁵², R⁵³, R⁵⁴ and R⁵⁵ are each independentlyselected from hydrogen, alkyl, substituted alkyl, a polyether moiety,carboxyl, substituted carboxyl, carbamate, substituted carbonate,carbonyloxy, alkoxy, substituted alkoxy, haloalkyl, halogen, nitro,amino, aryloxy, cyano, hydroxyl, or sulfonyl.

In certain embodiments, R⁵¹ is halogen.

In certain embodiments, R²⁰ is hydrogen, lower alkyl, nitro, amino, orlower alkoxy.

In certain embodiments, R⁵², R⁵³, R⁵⁴ and R⁵⁵ are each hydrogen.

Alternative Y groups can be selected from

In certain embodiments of formula II, R¹⁵ is lower alkyl, particularlytert-butyl.

In certain embodiments of formula II, there are two R¹⁵ groups, each ina para position relative to the position of the —NH— group.

In certain embodiments of formula II, X is lower alkoxy, particularlymethoxy.

In certain embodiments of formula II, m is 1 and the X group is in apara position relative to the position of the —NH— group.

Illustrative receptor compounds include:

These compounds can be synthesized as described, for example, in U.S.Pat. Nos. 7,803,946 and 8,841,360 and U.S. Patent Publ. 2015-0355153-A1.

Exemplary receptor compounds exhibit ligand binding selectivity orrecognition. The host compounds may exhibit selectivity in binding ofHS⁻ or H₂S or reporting of HS⁻ or H₂S's presence. For example, aspectral property of a host compound, such as fluorescence, may shiftupon binding certain ligands, but not others. It has been demonstratedfor exemplary compounds disclosed herein that the spectral properties,such as the UV-Vis spectra shift noticeably upon binding of differentguests. For example, the extended conjugation inherent in2,6-bis(2-anilinoethynyl)pyridines derivatives produces distinctemission properties that will be used to monitor interactions with guestmolecules.

In certain embodiments, the receptor compound may be included within amembrane of an electronic device (e.g., field effect transistor,ion-selective electrode, microfluidic, electrochemical cell,pre-concentration membrane, lab-on-a-chip membrane/component, etc.) toprovide an electrical readout of the detection of H₂S or HS⁻.

In one embodiment, the receptor compound is included in a field effecttransistor (FET) device. An illustrative FET device 1 is shown in FIGS.5 and 6. When FETs are used as chemical sensors, they are usually calledChemFETs or ISFETs. An example FET is shown having the following fivecomponents: a source 2, a drain 3, a gate 4, a gate electrode 5, andbulk (or body) 6. The source 2 contacts a first portion of the bulk 6,and the drain 3 contacts a second portion of the bulk 6 that is locallydistinct from the first portion. A region 11 of the bulk separates thesource 2 from the drain 3. Gate 4 is disposed on a surface of the bulk 6in a position between the source 2 and drain 3. When a ChemFET or ISFET(or almost any FET-based sensor) is made, the gate electrode 5 isseparated in space from the gate 4. The gate electrode 5 becomes thereference electrode and in this configuration, those terms can be usedinterchangeably. The gate 4 and gate electrode 5 are the only componentsexposed to the sample environment. The source 2, drain 3, and bulk 6 areencapsulated or sealed off such as with an encapsulating polymer or SiO₂7.

A polymeric element 8 is disposed on a surface of the gate 4 thatopposes the gate/bulk interface. The polymeric element 8 may be apolymer-containing coating or layer. In other words, the gate 4 islocated between the polymeric element 8 and the bulk 6. The polymericelement 8 residing on the gate 4 (not on the gate electrode 5)determines the sensitivity and selectivity of the device. In general,the polymeric element 8 comprises at least three components. In certainembodiments, the polymeric element 8 consists of only a polymer, thereceptor compound(s) disclosed herein, and an ionophore (i.e, a salt).

One component is the polymer itself which may be, but is not limited to,a polyvinyl chloride, polyvinyl alcohol, polystyrene, butadienecopolymer, polysiloxane, epoxy acrylate, methacrylate, urethaneacrylate, polyacrylamide, among many others. In general, a suitablepolymer must have the following characteristics:

1) Good adhesion to the gate substrate (which is typically silicon oxideor silicon nitride).2) Good chemical resistance to other components and to common speciespresent in the environment of intended use. For example, a devicedesigned to detect hydrosulfide in water will require a polymer that isinert to hydrosulfide and water.3) Sufficient mechanical strength.4) Permeability to the target analyte.Processing requirements are also considered. Polymers may be processedby solvent casting or by polymerization directly on the device such asby photopolymerization of acrylates. Many classes of polymers listedabove require additives in order to achieve the requiredcharacteristics. For example, polyvinyl chloride must be highlyplasticized (a large amount of plasticizer must be added) in order forthe material to meet the requirements of the application. This isgenerally considered to be undesirable but it is often unavoidable.

The second component is the receptor compound(s) disclosed herein.

The third component is an ionophore that may be, but is not limited to,a salt such as tetraoctylammonium bromide which serves to make thepolymer coating more ionic and, thus, more hospitable to water andwater-soluble species like hydrosulfide. Salts typically have onecomponent ion of significance to the application and another which isrequired but incidental. For example, the tetraoctylammonium componentof tetraoctylammonium bromide, serves as a cationic feature of thematerial while the bromide is believed to exchange with other anions inthe sample medium and is not considered an important part of thedetection system. Tetraoctylammonium chloride works just as well. Theprimary characteristics of the salt are that the primary component beeffectively immobile in the polymer coating. Viewed another way, thesalt component should much more soluble in the polymer than it is inwater, where the device is intended to function in water. The salts alsohave to be inert to the other polymer components as well as to thetarget analyte and sample environment.

When the polymer coating needs to be made cationic, as is the case withhydrosulfide detection, tetralkylammonium salts such astetraoctylammonium or tetradodecylammonium are suitable. Lipophilic ionsare usually used since it is almost always the case that the polymer ismore lipophilic than the sample medium. This is the case with anyaqueous application of these devices.

The polymer itself accounts for most of the mass of the polymer coatingand the other components are incorporated at various ratios. Thereceptor is typically present in an amount of 0.1 to 5%, moreparticularly 0.1 to 1% by weight, based on the total weight of thepolymer coating. The salts are typically incorporated at 1% to 5% byweight, based on the total weight of the polymer coating. The polymeritself along with any required polymer additives (plasticizers, forexample) makes up the remainder of the polymer coating.

A data logger or data collection device 9 is coupled to a controlcircuit 10. The data collection device 9 may be any device used tointerpret and record an analog voltage.

Illustrative devices include Fluke RMS multimeters, National InstrumentsDAQ devices, and other analog-to-digital conversion instruments.

The control circuit 10, also called the interface circuit, is associatedwith each individual chemical sensor 1 and is required to obtain ameasurement signal from the chemical sensor. There are many possibleconfigurations and operational modes for control circuits. Anillustrative control circuit is known as “Voltage Feedback to theReference Electrode.” In short, this operates by maintaining constantvoltage and from source to drain (source and drain are features of thechemical sensor, when that sensor is a FET device) as well as a constantdrain current while allowing the reference electrode voltage to float.This voltage at the reference electrode is taken as the measurementsignal and relates linearly to the log of the concentration of thetarget species (hydrosulfide in this case).

The reference electrode 5, when the chemical sensor is a FET device, isthe gate electrode. There are multiple options for reference electrodematerial and form factor, including, for example, gold pins and Ag/AgClreference electrodes.

The reference electrode and chemical sensor are immersed in an aqueoussolution containing the analyte of interest (e.g., hydrosulfide). Thenthe control circuit is powered and, when the output voltage is stable,the voltage is taken as the measurement signal. Stable voltage istypically achieved within one minute. In some cases, higher voltagecorresponds to higher concentrations of the target analyte, although therelationship can be reversed.

Illustrative embodiments of the methods and materials disclosed hereinare described in the numbered clauses below:

1. A method for detecting for the presence of H₂S or an anionic sulfidespecies in a system, comprising contacting a sample from the system witha compound, or a protonate or salt thereof, having a structurerepresented by:

wherein Y represents an aromatic group or a substituted aromatic group;

n is 1 or 2;

R is independently H, alkyl, substituted alkyl, a polyether moiety,carboxyl, substituted carboxyl, carbamate, substituted carbonate,carbonyloxy, alkoxy, substituted alkoxy, haloalkyl, halogen, nitro,amino, amido, aryloxy, cyano, hydroxyl, or sulfonyl;

R¹ is H, substituted lower alkyl, lower alkyl, substituted aralkyl oraralkyl;

R² is selected from H, acyl, substituted aralkyl, aralkyl, phosphonyl,—SO₂R³; —C(O)R⁵; —C(O)OR⁷ or —C(O)NR⁹R¹⁰;

R³; R¹; R⁷; R⁹ and R¹⁰ are each independently selected from H,substituted lower alkyl, lower alkyl, substituted aralkyl, aralkyl,substituted aryl or aryl.

2. A method for detecting for the presence of H₂S or an anionic sulfidespecies in a system, comprising contacting a sample from the system witha compound, or a protonate or salt thereof, having a structurerepresented by:

wherein Y represents a substituted aromatic group or an aromatic group;

each R¹⁵ is independently H, alkyl, substituted alkyl, a polyethermoiety, carboxyl, substituted carboxyl, carbamate, substitutedcarbonate, carbonyloxy, alkoxy, substituted alkoxy, haloalkyl, halogen,nitro, amino, amido, aryloxy, cyano, hydroxyl, or sulfonyl;

each X is independently halogen, alkoxy, substituted alkoxy, alkyl,substituted alkyl or a polyether moiety; and

m is 0 to 5.

3. The method of clause 1 or 2, wherein the system comprises an aqueoussystem.

4. The method of clause 1 or 2, wherein the system comprises abiological system.

5. The method of any one of clauses 1 to 4, wherein Y is selected from:

wherein R²⁰, R⁵⁰, R⁵¹, R⁵², R³, R⁴ and R⁵⁵ are each independentlyselected from hydrogen, alkyl, substituted alkyl, a polyether moiety,carboxyl, substituted carboxyl, carbamate, substituted carbonate,carbonyloxy, alkoxy, substituted alkoxy, haloalkyl, halogen, nitro,amino, aryloxy, cyano, hydroxyl, or sulfonyl.

6. The method of clause 5, wherein Y is

wherein R⁵⁰ is halogen.

7. The method of clause 5, wherein Y is

wherein R²⁰ is hydrogen.

8. A method for detecting for the presence of H₂S or an anionic sulfidespecies in a system, comprising contacting a sample from the system witha compound, or a protonate or salt thereof, having a structure thatincludes at least one moiety configured for reversible, non-covalentbinding of the anionic sulfide species.

9. The method of clause 8, wherein the reversible, non-covalent bondinginvolves hydrogen bonding.

10. The method of clause 9, wherein the hydrogen bonding includes a C—H. . . S hydrogen bond.

11. The method of clause 8, wherein the at least one moiety is a CHhydrogen bond donor.

12. A compound, or a protonate or salt thereof, having a structurerepresented by:

wherein Y is

each R¹⁵ is independently H, alkyl, substituted alkyl, a polyethermoiety, carboxyl, substituted carboxyl, carbamate, substitutedcarbonate, carbonyloxy, alkoxy, substituted alkoxy, haloalkyl, halogen,nitro, amino, amido, aryloxy, cyano, hydroxyl, or sulfonyl;

each X is independently halogen, alkoxy, substituted alkoxy, alkyl,substituted alkyl or a polyether moiety;

m is 0 to 5; and

wherein R⁵⁰, R⁵¹, R⁵², R⁵³, R⁵⁴ and R⁵⁵ are each independently selectedfrom hydrogen, alkyl, substituted alkyl, a polyether moiety, carboxyl,substituted carboxyl, carbamate, substituted carbonate, carbonyloxy,alkoxy, substituted alkoxy, haloalkyl, halogen, nitro, amino, aryloxy,cyano, hydroxyl, or sulfonyl.

13. The compound of clause 12, wherein Y is

and R⁵⁰ is halogen and R⁵¹ is hydrogen.

14. The compound of clause 12, wherein Y is

and R⁵², R⁵³, R⁵⁴ and R⁵⁵ are each hydrogen.

15. The compound of any one of clauses 12 to 14, wherein each R¹⁵ isalkyl; m is 1, and X is alkoxy.

EXAMPLES

To investigate whether HS⁻ is a suitable anionic guest for compounds1-3, we titrated NBu₄SH into 0.5-1.0 mM solution of each host in 10%DMSO-d₆/CD₃CN and monitored the titrations by ¹H NMR spectroscopy. Ineach case, we observed that the urea NH resonances shifted significantlydownfield upon HS⁻ addition, consistent with anion binding (FIG. 2). Forexample, upon addition of HS⁻ to a 0.988 mM solution of 1, the arylCH_(a) shifted from 7.99 to 9.24 ppm, and the NH_(b) and NH_(c) ureaprotons shift downfield from 7.94 and 8.92 to 8.63 and 11.18 ppm,respectively. Highlighting the preference of 1-3 for HS⁻ rather thanH₂S, addition of H₂S gas to any of the receptors failed to change theUV-Vis or NMR spectra of the hosts. We also confirmed that the observedchanges in the NMR spectra upon HS⁻ addition were not merely due todeprotonation of the urea NH groups. Addition of the strong base1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) produced significantlydifferent UV-Vis and NMR spectra than those observed upon HS⁻ addition.On the basis of the high nucleophilicity of HS⁻, we also wanted toconfirm that the anion did not irreversibly modify the alkyne moietiesof the host scaffolds. Monitoring the ¹³C{¹H} NMR spectrum of a 2.3 mMsolution of 1 before and after addition of 10 equivalents of HS⁻confirmed that the alkynes were unreactive toward HS⁻. Titration data ofHS⁻ with the host fit to simple 1:1 binding isotherm models, and a new,upfield-shifted peak appears for bound hydrosulfide. Taken together,these results support the hypothesis that HS⁻ acts an anionic guestwithin the pocket of the host, rather than covalently modifying the hostscaffold.

To determine whether receptors 1-3 exhibited selectivity for HS⁻ overother similar anions, we performed comparison titrations with NBu4Clunder identical conditions. Using 1H NMR titration data, we establishedthat pyridine-based hosts 2 and 3 overall had significantly lowerbinding constants for both anions than did phenyl core host 1. Thisdifference is likely due to the extra CH hydrogen bond donated from thephenyl core; however, it does not meet our initial hypothesis that HS⁻should also act as a weak hydrogen bond donor to an acceptor (e.g.,pyridine nitrogen) on the host receptor (2-3). Despite the lower bindingaffinities, the pyridine-based hosts 2 and 3 exhibited 6-foldselectivity for HS⁻ over Cl⁻, whereas host 1 exhibited 2.8-foldselectivity. The higher selectivity is likely due to the pyridine lonepair acting as a hydrogen bond acceptor, which provides an additionalstabilizing interaction for HS⁻ and a destabilizing interaction for Cl⁻.The phenyl core of host 1 donates a hydrogen bond to both anionicguests, resulting in decreased selectivity for hydrosulfide, even ifthis CH hydrogen bond is an important component to the high overallbinding energy.

To further investigate the difference in anion selectivity, bindingconstants were also measured at lower concentrations by UV-Visspectroscopy in MeCN; the data are summarized in Table 1.

TABLE 1 HS⁻ and Cl⁻ Binding Parameters in Hosts 1-3. HS⁻ (log(K_(a)))Cl⁻ (log(K_(a))) Host Solvent ΔG (kcal mol⁻¹) ΔG (kcal mol⁻¹) 1 10%DMSO-d₆/CD₃CN 3.70 ± 0.07^(a) 3.25 ± 0.03^(a) −5.05 −4.43 MeCN 4.96 ±0.04^(b) 4.53 ± 0.07^(b) −6.76 −6.18 2 10% DMSO-d₆/CD₃CN 3.04 ± 0.06^(a)2.34 ± 0.07^(a) −4.15 −3.19 MeCN 4.30 ± 0.07^(b) 3.19 ± 0.07^(b) −5.86−4.35 3 10% DMSO-d₆/CD₃CN 3.12 ± 0.07^(a) 2.34 ± 0.02^(a) −4.25 −3.19MeCN 4.45 ± 0.07^(b) 3.08 ± 0.06^(b) −6.07 −4.20 ^(a)Fitting NMRspectroscopy data. ^(b)Fitting UV-Vis spectroscopy data.We expected that removal of the DMSO co-solvent would increase theobserved binding affinities since acetonitrile is a slightly lesscompetitive solvent (especially as a hydrogen bond acceptor). Additionof NBu₄SH to a 10 μM solution of 1, 2, or 3 resulted in attenuation ofthe 330 nm absorbance with concomitant increase at 360 nm, whileproceeding through a well-anchored isosbestic point near 350 nm. Asexpected, removal of the DMSO co-solvent produced significantly higherbinding affinities, with host 1 having a binding constant of 90,300 M⁻¹and hosts 2 and 3 providing binding constants of ˜25,000 M¹. In the caseof 1, the selectivity for HS¹ over Cl⁻ remained similar to the 10%DMSO-d₆/CD₃CN system, whereas in the case of the pyridine core, asignificant increase in selectivity is observed (˜18.5:1 HS⁻:Cl⁻). Theincrease in analyte selectivity is primarily due to changes in bindingenergy of the chloride host-guest system. The difference between thebinding energy of HS⁻ with 1 and 2 is the same in both solvents(ΔΔG=0.90 kcal mol⁻¹). In contrast, the Cl⁻ binding energy difference issolvent dependent with a larger change in pure acetonitrile (ΔΔG=1.24(DMSO/CH₃CN) vs. 1.83 (CH3CN) kcal mol⁻¹). In the case of HS⁻, the ΔΔGis the difference between two stabilizing hydrogen bond motifs and leadsto an estimate that a C—H . . . S hydrogen bond is up to 0.90 kcal mol⁻¹stronger than an S—H . . . N hydrogen bond. The ΔΔG of Cl⁻ binding islarger because this represents the difference between a small repulsiveN: . . . Cl contact and an attractive C—H . . . Cl hydrogen bond.

To further demonstrate the reversibility of HS⁻ binding, we treated a1.0 mM solution of 1 in 10% DMSO-d₆/CD₃CN (FIG. 3a ) with 2 equivalentsof NBu₄SH to form the HS⁻ bound adduct (FIG. 3b ), after which 4equivalents of Zn(OAc)₂ were added. Addition of the Zn(II) salt rapidlyresulted in precipitation of ZnS and regenerated the proton NMR spectrumcorresponding to free 1 (FIG. 3c ). Addition of 5 more equivalents ofNBu₄SH at the end of the reaction regenerated the HS⁻ host-guestcomplex, confirming the reversibility of binding in this scaffold.Importantly, the ¹³C{¹H} resonances of the alkyne carbons did not shiftsignificantly, confirming that there was no covalent modification of thereceptor scaffold.

Single crystals of [1.HS⁻ ][NBu₄+] were grown by layering n-hexanes ontoan equimolar solution of 1 and NBu₄SH in THF in a glovebox. [1.HS⁻][NBu₄+] crystallizes in the space group Pna21 with one molecule of THFper unit cell. Consistent with the solution NMR data, the HS⁻ occupiesthe binding pocket created by an aryl proton and four urea protons withthe NBu₄ ⁺ cation sitting just above the sulfide-phenyl core plane. Thestructure shows five hydrogen bonds from the host to the bound sulfideguest. The C—H . . . S hydrogen bond (3.711 Å) is longer than thoseformed between the distal bis(urea) protons (3.277, 3.281 Å) (FIG. 4a ).The average of all five hydrogen bond distances from the host to theguest is 3.56 Å, and all fall within previously defined criteria forhydrogen bonds. The host conformation in [1.HS⁻ ] is remarkably similarto the previously published chloride-bound structure, with an RMSdistance between the two structures of only 0.184 Å. These datademonstrate the similar recognition geometries required for Cl⁻ and HS⁻binding, again highlighting the potential for HS⁻ to be a potentialsubstrate for classical Cl⁻ binding domains in both native and syntheticsystems.

In view of the many possible embodiments to which the principles of thedisclosed compositions and methods may be applied, it should berecognized that the illustrated embodiments are only preferred examplesof the invention and should not be taken as limiting the scope of theinvention.

What is claimed is:
 1. A compound, or a protonate or salt thereof,having a structure represented by:

wherein Y is

each R¹⁵ is independently H, alkyl, substituted alkyl, a polyethermoiety, carboxyl, substituted carboxyl, carbamate, substitutedcarbonate, carbonyloxy, alkoxy, substituted alkoxy, haloalkyl, halogen,nitro, amino, amido, aryloxy, cyano, hydroxyl, or sulfonyl; each X isindependently halogen, alkoxy, substituted alkoxy, alkyl, substitutedalkyl or a polyether moiety; m is 0 to 5; and wherein R⁵⁰, R⁵¹, R⁵²,R⁵³, R⁵⁴ and R⁵⁵ are each independently selected from hydrogen, alkyl,substituted alkyl, a polyether moiety, carboxyl, substituted carboxyl,carbamate, substituted carbonate, carbonyloxy, alkoxy, substitutedalkoxy, haloalkyl, halogen, nitro, amino, aryloxy, cyano, hydroxyl, orsulfonyl.
 2. The compound of claim 1, wherein Y is

and R⁵⁰ is halogen and R⁵¹ is hydrogen.
 3. The compound of claim 1,wherein Y is

and R⁵², R⁵³, R⁵⁴ and R⁵⁵ are each hydrogen.
 4. The compound of claim 1,wherein each R¹⁵ is alkyl; m is 1, and X is alkoxy.
 5. A devicecomprising: a source; a drain; a gate; a bulk layer, wherein the sourcecontacts a first portion of the bulk, and the drain contacts a secondportion of the bulk that is physically distinct from the first portionand the gate is disposed on a surface of the bulk in a position betweenthe source and the drain forming a gate/bulk interface; and a polymericelement disposed on a surface of the gate that opposes the gate/bulkinterface, wherein the polymeric element comprises a (A) polymer and(B)(i) a compound, or a protonate or salt thereof, having a structurerepresented by:

wherein Y represents an aromatic group or a substituted aromatic group;n is 1 or 2; R is independently H, alkyl, substituted alkyl, a polyethermoiety, carboxyl, substituted carboxyl, carbamate, substitutedcarbonate, carbonyloxy, alkoxy, substituted alkoxy, haloalkyl, halogen,nitro, amino, amido, aryloxy, cyano, hydroxyl, or sulfonyl; R¹ is H,substituted lower alkyl, lower alkyl, substituted aralkyl or aralkyl; R²is selected from H, acyl, substituted aralkyl, aralkyl, phosphonyl,—SO₂R³; —C(O)R⁵; —C(O)OR⁷ or —C(O)NR⁹R¹⁰; R³; R⁵; R⁷; R⁹ and R¹⁰ areeach independently selected from H, substituted lower alkyl, loweralkyl, substituted aralkyl, aralkyl, substituted aryl or aryl; or(B)(ii) a compound, or a protonate or salt thereof, having a structurerepresented by:

wherein Y represents a substituted aromatic group or an aromatic group;each R¹⁵ is independently H, alkyl, substituted alkyl, a polyethermoiety, carboxyl, substituted carboxyl, carbamate, substitutedcarbonate, carbonyloxy, alkoxy, substituted alkoxy, haloalkyl, halogen,nitro, amino, amido, aryloxy, cyano, hydroxyl, or sulfonyl; each X isindependently halogen, alkoxy, substituted alkoxy, alkyl, substitutedalkyl or a polyether moiety; and m is 0 to
 5. 6. The device of claim 5,wherein Y is

wherein R⁵⁰, R⁵¹, R⁵², R⁵³, R⁵⁴ and R⁵⁵ are each independently selectedfrom hydrogen, alkyl, substituted alkyl, a polyether moiety, carboxyl,substituted carboxyl, carbamate, substituted carbonate, carbonyloxy,alkoxy, substituted alkoxy, haloalkyl, halogen, nitro, amino, aryloxy,cyano, hydroxyl, or sulfonyl.
 7. The device of claim 5, wherein thepolymer is selected from at least one of a polyvinyl chloride, polyvinylalcohol, polystyrene, butadiene copolymer, polysiloxane, epoxy acrylate,methacrylate, urethane acrylate, polyacrylamide, or a combinationthereof.
 8. The device of claim 5, wherein the polymeric element furthercomprises at least one ionophore.
 9. The device of claim 8, wherein theionophore comprises at least one tetralkylammonium salt.
 10. The deviceof claim 5, wherein the compound (B)(i) or the compound (B)(ii) ispresent in the polymeric element in an amount of 0.1 to 5% by weight,based on the total weight of the polymeric element.
 11. A devicecomprising: a source; a drain; a gate; a bulk layer, wherein the sourcecontacts a first portion of the bulk, and the drain contacts a secondportion of the bulk that is locationally distinct from the first portionand the gate is disposed on a surface of the bulk in a position betweenthe source and the drain forming a gate/bulk interface; and a polymericelement disposed on a surface of the gate that opposes the gate/bulkinterface, wherein the polymeric element comprises a (A) polymer and acompound, or a protonate or salt thereof, having a structure thatincludes at least one moiety configured for reversible, non-covalentbinding of the anionic sulfide species.
 12. The device of claim 11,wherein the reversible, non-covalent bonding involves hydrogen bonding.13. The device of claim 12, wherein the hydrogen bonding includes a C—H. . . S hydrogen bond.
 14. The device of claim 11, wherein the at leastone moiety is a CH hydrogen bond donor.